Prinsip Asas Tindakan Dadah

(NFNF1022)
SEMESTER II 2018-2019

ROUTE OF
ADMINISTRATION

PRACTICAL REPORT

Name : Haikal Ishigaki Bin Abd Karim Ishigaki

Matric No.: A168659
Group: Group 8
Date: 20/3/2019
Title: Routes of Administration
Introduction:
In pharmacology, route of administration refers to the path that being taken by the drug
into our body. The determination of the route of administration is govern by two factors which
are the properties of the drugs and also the therapeutic objectives. There are several major
routes of administration of drug include enteral, parenteral and topical. Enteral is usually where
the drug is administered by the mouth either the patient will swallow it or being placed under
the tongue. This route is the most common, convenient and economical method. However, this
route may be not suitable for drugs that not stable with the stomach’s pH. Hence, here comes
another route of administration which is parenteral route. This route will prevent the drugs from
passing the first-pass hepatic metabolism. Parenteral routes include intravenous (IV),
intramuscular (IM), subcutaneous (SC), and intraperitoneal (IP).

1. State your hypothesis for this experiment.

The effectiveness of drug is highest via intravenous then followed by intramuscular,
intraperitoneal, subcutaneous and the lowest effectiveness of drug is via oral
administration.
2. Describe the methodology of this experiment.
a) Intravenous
1. The mice labelled as 1 was lifted by the base of the tail and placed on the cage lid
with one hand and its tail was pulled gently back.
2. The scruff of the mice's neck behind the ears was fondled if the mice is tensed up.
3. The mice was then lifted from the cage lid by holding its' tail and it was placed into
the restrainer. A stopper was used to prevent the mice from escaping.
4. The amount of drug to be injected into the mice intravenously was calculated based
on the weight of the mice. The dosage of the drug to be injected was 0.1mg / 10g.
5. The syringe was used to suck up the drug from the reagent bottle and the needle
was inserted onto the front of the syringe.
6. Its' tail, which is the area for administration, was cleaned with alcohol-moistened
cotton.
7. Administration of drug was made into the lateral tail vein of the mice but not the
dorsal tail vein.
8. It was made sure that the needle was injected parallel to the tail vein.
9. It was observed whether some of the mice's blood enter the syringe while drug was
being administered into its lateral tail vein. If it can be observed, the administration of
drug is successful. No resistance should be felt too if the solution was properly
administered.
10. If administration of drug is unsuccessful, the administration was repeated.
11. After the drug had been successfully administered into the mice, the mice was
removed from the restrainer and the time of drug administration was recorded.
12. The time of onset of action and time when righting reflex return were recorded.
13. The onset of action and duration of action were calculated
b) Intraperitoneum
1. The mice labelled as 1 was lifted by the base of the tail and placed on the cage lid
with one hand and its tail was pulled gently back.
2. The scruff of the mice's neck behind the ears was fondled if the mice was tensed
up.
3. The mice is manually restrained by another person and was held in a supine position
with its posterior end slightly elevated or the head can be tilted lower than the body.
4. The amount of drug to be injected into the mice intraperitoneumly was calculated
based on the weight of the mice. The dosage of the drug to be injected was 0.1mg / 10g.
5. The syringe was used to suck up the drug from the reagent bottle and the needle
was inserted onto the front of the syringe.
6. The intraperitoneal injection to the mice was made to the lower left quadrant of the
mice.
7. During administration of drugs, the needle and syringe were kept almost parallel to
its vertebral column to avoid accidental penetration of viscera.
8. The needle was pushed in at an approximately 10˚ angle between the needle and
the abdominal surface in the lower quadrant of the abdomen.
9. After the drug had been successfully administered into the mice, the time of drug
administration was recorded.
10. The time of onset of action and time when righting reflex return were recorded.
11. The onset of action and duration of action were calculated.

c) Intramuscular
1. The mice labelled as 1 was lifted by the base of the tail and placed on the cage lid
with one hand and its tail was pulled gently back.
2. The scruff of the mice's neck behind the ears was fondled if the mice is tensed up.
3. The mice was manually restrained by another person and was held in a supine
position with its posterior end slightly elevated or the head can be tilted lower than the
body.
4. The amount of drug to be injected into the mice intramuscularly was calculated
based on the weight of the mice. The dosage of the drug to be injected was 0.1mg / 10g.
5. The syringe was used to suck up the drug from the reagent bottle and the needle
was inserted onto the front of the syringe.
6. The needle tip was inserted through the skin and into the muscle.
7. After the drug had been successfully administered into the mice, the time of drug
administration was recorded.
8. The time of onset of action and time when righting reflex return were recorded.
9. The onset of action and duration of action were calculated

d) Subcutaneous
1. The mice labelled as 1 was lifted by the base of the tail and placed on the cage lid
with one hand and its tail was pulled gently back.
2. The scruff of the mice's neck behind the ears was fondled if the mice is tensed up.
3. The mice was manually restrained by another person.
4. The amount of drug to be injected into the mice subcutaneously was calculated
based on the weight of the mice. The dosage of the drug to be injected was 0.1mg / 10g.
5. The syringe was used to suck up the drug from the reagent bottle and the needle
was inserted onto the front of the syringe.
 6. The needle was inserted under the skin of the interscapular area tented by the thumb
and forefinger. The drug was then injected.
7. After the drug had been successfully administered into the mice, the time of drug
administration was recorded.
8. The time of onset of action and time when righting reflex return were recorded.
9. The onset of action and duration of action were calculated.

e) Oral
1. The mice labelled as 1 was lifted by the base of the tail and placed on the cage lid
with one hand and its tail was pulled gently back.
2. The scruff of the mice's neck behind the ears was fondled if the mice is tensed up.
3. The mice was manually restrained.
4. The amount of drug to be injected into the mice intramuscularly was calculated
based on the weight of the mice. The dosage of the drug to be injected was 0.1mg / 10g.
5. The syringe was used to suck up the drug from the reagent bottle and the gavage
needle was inserted onto the front of the syringe. (A gavage needle or ball tip needle
was used to prevent damaging the esophagus and from passing through the glottal
opening into the trachea.)
6. After the drug had been successfully administered into the mice orally, the time of
drug administration was recorded.
7. The time of onset of action and time when righting reflex return were recorded.
8. The onset of action and duration of action were calculated

3. How do the mice react towards the drug?

After a few time from the time of the drug is given via intravenous or intramuscular or
intraperitoneal or subcutaneous or oral, the mice lack of spontaneous activity. After
that, the mice is loss of righting reflex. This is the time of onset of action. After some
time, the mice has its' righting reflex return.
 4. Calculate the average and standard deviation (SD) of your data (collect from other
group AND choose EITHER the onset of action OR duration of action). Show your
calculation. What does it mean by SD?

Route of administration: Intravenous

Mice Body Dose Time of drug Time of Time Onset of Duration

weight (mL) administration onset of when action of action
(g) action righting (minutes) (minutes)
reflex
return
1 29 0.29 4.14 p.m. 4.17 p.m. 4.25 p.m. 3 8

2 27 0.27 3.22 p.m. 3.23 p.m. 3.36 p.m. 1 13

3 30 0.3 2.54 p.m. 2.54 p.m. 3.04 p.m. 0 10

4 32 0.32 3.15 p.m. 3.16 p.m. 3.30 p.m. 1 14

5 31 0.31 3.30 p.m. 3.30 p.m. 3.37 p.m. 0 7

6 33 0.33 3.52 p.m. 3.52 p.m. 4.01 p.m. 0 9

7 30 0.3 3.33 p.m. 3.35 p.m. 3.47 p.m. 2 12

8 30 0.3 3.12 p.m. 3.12 p.m. 3.26 p.m. 0 14
9 32 0.32 3.15 p.m. 3.17 p.m. 3.31 p.m. 2 14
10 32 0.32 2.50 p.m. 2.54 p.m. 3.06 p.m. 4 12
1.3 11.3
Average
1.41 2.57
Standard deviation (SD)

(8+13+10+14+7+9+12+14+14+12)
Average duration of action (minutes) = 10

= 11.3 minutes
(3+1+0+1+0+0+2+0+2+4)
Average onset of action (minutes) =
10

= 1.3 minutes
 = (8 – 11.3)2 + (13 – 11.3)2 + (10 – 11.3)2 + (14 – 11.3)2
+ (7 – 11.3)2 + (9 – 11.3)2 + (12 – 11.3)2 + (14 – 11.3)2 + (14 – 11.3)2
+ (12 – 11.3)2
= 59.61

1
Standard deviation of action (minutes) = √10−1 √59.61

= 2.57 minutes

= (3 – 1.3)2 + (1 – 1.3)2 + (0 – 1.3)2 + (1 – 1.3)2

+ (0 – 1.3)2 + (0 – 1.3)2 + (2 – 1.3)2 + (0 – 1.3)2 + (2 – 1.3)2
+ (4 – 1.3)2
= 18.1

1
Standard onset of action (minutes) = √10−1 √18.1

= 1.41 minutes
 Route of administration: Intramuscular

Mice Body Dose Time of drug Time of Time Onset of Duration

weight (mL) administration onset of when action of action
(g) action righting (minutes) (minutes)
reflex
return
1 33 0.33 3.02 p.m. 3.06 p.m. 3.24 p.m. 4 18

2 32 0.32 3.10 p.m. 3.12 p.m. 3.20 p.m. 2 8

3 29 0.29 3.17 p.m. 3.24 p.m. 3.28 p.m. 7 4

4 30 0.3 2.44 p.m. 3.08 p.m. 3.09 p.m. 24 1

5 30 0.3 3.25 p.m. 3.30 p.m. 3.37 p.m. 5 7

6 23 0.23 4.02 p.m. 4.21 p.m. 4.22 p.m. 19 1

7 30 0.3 3.40 p.m. 4.02 p.m. 4.05 p.m. 22 3

8 35 0.35 2.50 p.m. 2.55 p.m. 3.01 p.m. 5 6
9 30 0.3 2.45 p.m. 2.52 p.m. 2.57 p.m. 7 5
10 31 0.31 2.58 p.m. 3.01 p.m. 3.14 p.m. 3 13
9.8 6.6
Average
8.41 5.35
Standard deviation (SD)

(18+8+4+1+7+1+3+6+5+13)
Average duration of action (minutes) = 10

= 6.6 minutes
(4+2+7+24+5+19+22+5+7+3)
Average onset of action (minutes) = 10

= 9.8 minutes
 = (18 – 6.6)2 + (8 – 6.6)2 + (4 – 6.6)2 + (1 – 6.6)2
+ (7 – 6.6)2 + (1 – 6.6)2 + (3 – 6.6)2 + (6 – 6.6)2 + (5 – 6.6)2
+ (13 – 6.6)2
= 258.4

1
Standard deviation of action (minutes) = √10−1 √258.4

= 5.35 minutes

= (4 – 9.8)2 + (2 – 9.8)2 + (7 – 9.8)2 + (24 – 9.8)2

+ (5 – 9.8)2 + (19 – 9.8)2 + (22 – 9.8)2 + (5 – 9.8)2 + (7 – 9.8)2
+ (3 – 9.8)2
= 637.6

1
Standard onset of action (minutes) = √10−1 √637.6

= 8.41 minutes
 Route of administration: Intraperitoneum

Mice Body Dose Time of drug Time of Time Onset of Duration

weight (mL) administration onset of when action of action
(g) action righting (minutes) (minutes)
reflex
return
1 34 0.34 3.27 p.m. 3.40 p.m. 3.49 p.m. 13 9

2 26 0.26 3.46 p.m. 3.56 p.m. 4.11 p.m. 10 15

3 29 0.29 3.24 p.m. 3.29 p.m. 3.50 p.m. 5 21

4 29 0.29 2.58 p.m. 3.03 p.m. 3.05 p.m. 5 2

5 22 0.22 2.39 p.m. 2.46 p.m. 2.50 p.m. 7 4

6 27 0.27 3.01 p.m. 3.05 p.m. 3.15 p.m. 4 10

7 27 0.27 3.20 p.m. 3.25 p.m. 3.31 p.m. 5 6

8 29 0.29 3.35 p.m. 3.42 p.m. 3.52 p.m. 7 10
9 31 0.31 3.05 p.m. 3.15 p.m. 3.35 p.m. 10 20
10 32 0.32 3.00 p.m. 3.08 p.m. 3.18 p.m. 8 10
7.4 10.7
Average
2.88 6.31
Standard deviation (SD)

(9+15+21+2+4+10+6+10+20+10)
Average duration of action (minutes) = 10

= 10.7 minutes
(13+10+5+5+7+4+5+7+10+8)
Average onset of action (minutes) = 10

= 7.4 minutes
 = (9 – 10.7)2 + (15 – 10.7)2 + (21 – 10.7)2 + (2 – 10.7)2
+ (4 – 10.7)2 + (10 – 10.7)2 + (6 – 10.7)2 + (10 – 10.7)2 + (20 – 10.7)2
+ (10 – 10.7)2
= 358.1

1
Standard deviation of action (minutes) = √10−1 √358.1

= 6.31 minutes

= (13 – 7.4)2 + (10 – 7.4)2 + (5 – 7.4)2 + (5 – 7.4)2

+ (7 – 7.4)2 + (4 – 7.4)2 + (5 – 7.4)2 + (7 – 7.4)2 + (10 – 7.4)2
+ (8 – 7.4)2
= 74.4

1
Standard onset of action (minutes) = √10−1 √74.4

= 2.88 minutes
 Route of administration: subcutaneous

Mice Body Dose Time of drug Time of Time Onset of Duration

weight (mL) administration onset of when action of action
(g) action righting (minutes) (minutes)
reflex
return
1 37 0.37 2.41 p.m. 2.47 p.m. 3.02 p.m. 6 15

2 32 0.32 2.57 p.m. 3.01 p.m. 3.07 p.m. 4 6

3 34 0.34 2.47 p.m. 2.54 p.m. 3.04 p.m. 7 10

4 36 0.36 2.52 p.m. 3.35 p.m. 3.37 p.m. 43 2

5 35 0.35 2.38 p.m. 3.00 p.m. 3.01 p.m. 22 1

6 28 0.28 3.33 p.m. 4.02 p.m. 4.05 p.m. 29 3

7 26 0.26 2.54 p.m. 3.19 p.m. 3.23 p.m. 25 4

8 32 0.32 2.57 p.m. 3.01 p.m. 3.05 p.m. 4 4
9 32 0.32 2.54 p.m. 3.15 p.m. 3.19 p.m. 21 4
10 31 0.31 3.17 p.m. 3.22 p.m. 3.30 p.m. 5 8
16.6 5.7
Average
13.4 4.24
Standard deviation (SD)

(15+6+10+2+1+3+4+4+4+8)
Average duration of action (minutes) = 10

= 5.7 minutes
(6+4+7+43+22+29+25+4+21+5)
Average onset of action (minutes) = 10

= 16.6 minutes
 = (15– 5.7)2 + (6 – 5.7)2 + (10 – 5.7)2 + (2 – 5.7)2
+ (1 – 5.7)2 + (3 – 5.7)2 + (4 – 5.7)2 + (4 – 5.7)2 + (4 – 5.7)2
+ (8 – 5.7)2
= 162.1

1
Standard deviation of action (minutes) = √10−1 √162.1

= 4.24 minutes

= (6 – 16.6)2 + (4 – 16.6)2 + (7 – 16.6)2 + (43 – 16.6)2

+ (22 – 16.6)2 + (29 – 16.6)2 + (25 – 16.6)2 + (4 – 16.6)2 + (21 – 16.6)2
+ (5 – 16.6)2
= 1626.4

1
Standard onset of action (minutes) = √10−1 √1626.4

= 13.4 minutes
 Route of administration: oral

Mice Body Dose Time of drug Time of Time Onset of Duration

weight (mL) administration onset of when action of action
(g) action righting (minutes) (minutes)
reflex
return
1 30 0.3 3.20 p.m. 3.30 p.m. 3.48 p.m. 10 18

2 36 0.36 4.03 p.m. 4.10 p.m. 4.20 p.m. 7 10

3 27 0.27 3.46 p.m. 3.51 p.m. 4.01 p.m. 5 10

4 25 0.25 3.09 p.m. 3.19 p.m. 3.31 p.m. 10 12

5 26 0.26 3.44 p.m. 3.46 p.m. 3.54 p.m. 2 8

6 22 0.22 3.15 p.m. 3.22 p.m. 3.32 p.m. 7 10

7 28 0.28 3.26 p.m. 3.34 p.m. 3.43 p.m. 8 9

8 29 0.29 3.28 p.m. 3.35 p.m. 3.42 p.m. 7 7
9 28 0.28 3.40 p.m. 3.50 p.m. 4.00 p.m. 10 10
10 26 0.26 2.32 p.m. 2.40 p.m. 2.50 p.m. 8 10
7.4 10.4
Average
2.50 2.99
Standard deviation (SD)

(18+10+10+12+8+10+9+7+10+10)
Average duration of action (minutes) = 10

= 10.4 minutes
(10+7+5+10+2+7+8+7+10+8)
Average onset of action (minutes) = 10

= 7.4 minutes
 = (18 – 10.4)2 + (10 – 10.4)2 + (10 – 10.4)2 + (12 – 10.4)2
+ (8 – 10.4)2 + (10 – 10.4)2 + (9 – 10.4)2 + (7 – 10.4)2 + (10 – 10.4)2
+ (10 – 10.4)2
= 80.4

1
Standard deviation of action (minutes) = √10−1 √80.4

= 2.99 minutes

= (10 – 7.4)2 + (7 – 7.4)2 + (5 – 7.4)2 + (10 – 7.4)2

+ (2 – 7.4)2 + (7 – 7.4)2 + (8 – 7.4)2 + (7 – 7.4)2 + (10 – 7.4)2
+ (8 – 7.4)2
= 56.4

1
Standard onset of action (minutes) = √10−1 √56.4

= 2.50 minutes

The standard deviation is a statistic that measures the dispersion of a dataset relative to its
mean and is calculated as the square root of the variance. It is calculated as the square root of
variance by determining the variation between each data point relative to the mean. If the data
points are further from the mean, there is a higher deviation within the data set, thus, the more
spread out the data, the higher the standard deviation.
5. Tabulate the average and SD for the onset of action and duration of action for all
routes of administration (gather results from other groups).

Routes of Average time Standard Average Standard

Administration of onset of deviation of duration of deviation of
action (min) time of onset of action (min) duration of
action (min) action (min)
Intravenous 1.3 1.41 11.3 2.57
Intramuscular 9.8 8.41 6.6 5.35
intraperitoneum 7.4 2.88 10.7 6.31
subcutaneous 16.6 13.4 5.7 4.24
oral 7.4 2.50 10.4 2.99

6. Generate a graph from the results in no. 4 above.

Average of time and standard deviation of onset of action

againts routes of administration
25
Average of time and SD of onset of

20

15
action (min)

10

0
Intravenous Intramuscular Intraperitoneum Subcetaneous Oral
-5
Routes of Administration

Average of time Standard deviation

 Average of time and standard deviation of duration of
action againts routes of administration
Average of time and SD of duration 14

12

10

8
of action (min)

0
Intravenous Intramuscular Intraperitoneum Subcetaneous Oral
Routes of Administration

Average of time Standard deviation

7. If you want to compare the duration of action between your RoA and another RoA
(e.g. oral vs intraperitoneal), what is the most suitable statistical analysis to be
performed on the data?

The most suitable analytical analysis is by using a graph of bioavailability.

Bioavailabilityis used to indicate the fraction (F) of the administered dose that reaches
the systemic circulations as intact drug, taking into account both absorption and local
metabolic degradation. F is measured by determining the plasma drug concentration
versus time curves in a group of subjects following oral and intravenous administration.
The areas under the plasma concentration time curves (AUC) are used to estimate F as
AUCoral/AUCintravenous. According to the graph, the higher the concentration of
drug in the blood plasma, the greater the effect of drug in the body.

8. State the conclusion of this experiment.

In conclusion, the experiments shown that different route of administration produce

different time of effects on the mice. The drugs have taken different duration of times
after the release of drugs to perform action. Intravenous show the fastest time for the
drug to react towards mice since it has the lowest value of standard deviation and also
shown higher consistency that shown in the graph. Hence, we can conclude that
intravenous is the best route to administer anesthetic drugs. Intravenous administration
is the best way to deliver a precise dose quickly and in a well-controlled manner
throughout the body. The hypothesis is accepted.
Discussion

Based on the experimental result above, the intravenous injection showed the fastest time
of onset duration. This is then follow by intraperitoneum injection, subcutaneous injection,
oral route and lastly the intramuscular injection. However, according to the theory, the
sequence of the route of administration with the least time of onset action should start with
intravenous, followed by intraperitoneum, intramuscular, subcutaneous and lastly followed
by oral route. Thus, the result shown is in correct order, except for the order between
intramuscular and oral administration as intramuscular is taking time longer compare to oral
administration where the drug take its effect. This shows that there are errors throughout
experiment for intramuscular. The error happened when the drug injected most probably
enter the the subcutaneous layer instead of the intramuscular route. This will cause the
slowing time of action. On top of that, the exact time for the mice to passed out may not be
accurately determined causing the time of onset action may be inaccurately recorded. In
short, the inaccuracies of the data for intramuscular is mainly due to the error when carrying
out injection and recording that data.

References
1. https://www.nature.com/articles/s41598-018-36897-w#Sec7
2. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-
science/routes-of-administration
3. https://www.investopedia.com/terms/s/standarddeviation.asp